Since its discovery in 1990, the tetraspanin superfamily (also known as TM4, 4TM, TM4SF, and tetraspans) has grown to include around 20 proteins [refs 1 & 2]. All of the members are cell-surface proteins that span the membrane four times, forming two extracellular loops. Some are found in organisms as primitive as schistosomes and nematodes.
The tetraspanins are diverse. Some are found in virtually all tissues (CD81, CD82, CD9, CD63), whereas others are highly restricted, such as CD37 (B cells) or CD53 (lymphoid and myeloid cells). Functionally, they are involved in diverse processes such as cell activation and proliferation, adhesion and motility, differentiation, and cancer. Many tetraspanins are being discovered as tumor-associated antigens, related to tumor growth and proliferation [2, 3]. This is in line with an emerging body of evidence indicating that tetraspanins are key players in the regulation of cell adhesion, proliferation, activation and migration. It has been proposed that all these functions may relate to the proteins' ability to act as ‘molecular facilitators’ which group specific cell-surface proteins and thus increase the formation and stability of functional signalling complexes.